P636: REAL WORLD OUTCOME WITH IBRUTINIB IN PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA FROM THE GERMAN REALITY STUDY
Authors: M. Welslau, R. Schlag, B. Heinrich, L. Vornholz, S. Buchholz, B. Marquard, S. Dörfel, G. Anke
Journal: HemaSphere (2022)

Background: Chronic lymphocytic leukemia (CLL) is one of the most common forms of leukemia, characterized by abnormal survival and proliferation of mature B cells in peripheral blood, bone marrow, and lymph nodes. Ibrutinib is a once-daily Bruton’s tyrosine kinase inhibitor (BTKi) with a significant benefit in both progression free survival (PFS) and overall survival (OS) demonstrated in multiple phase 3 trials for patients (pts) with previously untreated (1L) or relapsed/refractory (R/R) CLL. In 2014, ibrutinib was approved by the European Medicines Agency and made available to CLL pts in Germany. Prior to the REALITY study, limited data were available on the effectiveness of ibrutinib-treated pts with CLL in routine clinical practice in Germany. Aims: REALITY was a prospective, multicenter, non-interventional study to evaluate the effectiveness of ibrutinib as the 1st, 2nd, or ≥3rd line of treatment (cohorts C1, C2, and C3 respectively) in pts with CLL during the first 2 years of observation period in a real-world setting. Methods: 302 pts were enrolled in the three cohorts (C1: 104 pts; C2: 90 pts; C3: 108 pts) and treated in 57 study sites in Germany from January 2017 to July 2021. Written informed consent was obtained from all pts. Key study endpoints include retention rate (defined as ratio of pts on ibrutinib treatment to the number of pts at risk), start of next therapy, PFS, OS, and safety. The results of this study are descriptive, and no formal hypotheses was pre-specified. Results: Median age at time of ibrutinib treatment initiation was 74.0 years for the 1L pts in C1, and 72.5 and 73.0 years in the R/R cohorts of C2 and C3, respectively. In cohort C1 (1L), pts with genetic high risk features del(17p) and TP53 mutation were more frequent compared to C2 and C3. In C1 del(17p) was reported in 34/51 (66.7%) pts and TP53 mutations in 31/49 (63.3%) pts. In the R/R cohorts C2 and C3 del(17p) was reported in 11/57 (19.3%) pts and 13/65 (20.0%) pts, respectively. TP53 mutations were reported in 14/48 (29.2%) pts in C2 and 21/40 (52.5%) pts in C3. The primary study endpoint was retention rate, 77.9% pts continued to be on treatment after 1 year in C1 (1L). In C2 and C3 (R/R), the 1-year retention rates were 74.4% and 58.3% respectively. In C1, with median follow-up of 30.6 months, median PFS was not reached (NR). The 1-year PFS and OS in the C1 cohort (1L) were 91.3% and 96.2%, respectively. Only 8 pts initiated next line treatment in C1 after 1 year. In C2, with a median follow-up of 31.5 months, median PFS was NR. The 1-year PFS and OS were 85.6% and 93.3%, respectively. 11 pts initiated next line treatment in C2 after 1 year. In C3 median follow-up was 30.9 months and median PFS was NR. The 1-year PFS and OS were 83.3% and 93.5%, respectively. 26 pts initiated next line treatment in C3 after 1 year. Detailed results after 1 and 2 years of observation are summarized in Table 1. No new safety signals for ibrutinib were observed. Image:Summary/Conclusion: This first, comprehensive data from clinical practice of ibrutinib-treated pts with CLL in Germany showed that ibrutinib is a highly effective treatment option, especially as a 1st line treatment. The effectiveness and safety profile were consistent with clinical trials.